MDedge Dermatology

Key clinical point: Treating skin manifestations with biologics significantly reduced the risk of developing psoriatic arthritis (PsA) in patients with psoriasis.

Major finding: The risk of developing PsA was significantly higher in patients who did not receive treatment with biologics vs. the biological treatment group (adjusted hazard ratio 1.39; 95% CI 1.03-1.87).

Study details: Findings are from a retrospective cohort including 1,326 patients with psoriasis without PsA, of which 663 patients received biological treatment and 663 patients did not receive biological treatment.

Disclosures: This study did not report any external funding. Dr. Pavlovsky declared serving as investigator, advisor, consultant, and invited lecturer for various sources.

Source: Rosenthal YS et al. Arthritis Rheumatol. 2021 Aug 23. doi: 10.1002/art.41946.

Key clinical point: Treating skin manifestations with biologics significantly reduced the risk of developing psoriatic arthritis (PsA) in patients with psoriasis.

Major finding: The risk of developing PsA was significantly higher in patients who did not receive treatment with biologics vs. the biological treatment group (adjusted hazard ratio 1.39; 95% CI 1.03-1.87).

Study details: Findings are from a retrospective cohort including 1,326 patients with psoriasis without PsA, of which 663 patients received biological treatment and 663 patients did not receive biological treatment.

Disclosures: This study did not report any external funding. Dr. Pavlovsky declared serving as investigator, advisor, consultant, and invited lecturer for various sources.

Source: Rosenthal YS et al. Arthritis Rheumatol. 2021 Aug 23. doi: 10.1002/art.41946.

Key clinical point: Treating skin manifestations with biologics significantly reduced the risk of developing psoriatic arthritis (PsA) in patients with psoriasis.

Major finding: The risk of developing PsA was significantly higher in patients who did not receive treatment with biologics vs. the biological treatment group (adjusted hazard ratio 1.39; 95% CI 1.03-1.87).

Study details: Findings are from a retrospective cohort including 1,326 patients with psoriasis without PsA, of which 663 patients received biological treatment and 663 patients did not receive biological treatment.

Disclosures: This study did not report any external funding. Dr. Pavlovsky declared serving as investigator, advisor, consultant, and invited lecturer for various sources.

Source: Rosenthal YS et al. Arthritis Rheumatol. 2021 Aug 23. doi: 10.1002/art.41946.

Federal efforts to improve the quality, safety, and efficacy of over-the-counter sunscreens took a step forward today with the release of two orders aimed at updating regulatory requirements for most sunscreen products in the United States.

“We see it as a key public health priority and our regulatory obligation to make sure that marketed sunscreen products offer protection from the sun’s effects and that they deliver on those promises to consumers,” Theresa Michele, MD, director of the office of nonprescription drugs in the FDA’s Center for Drug Evaluation and Research, said during a media briefing.

When the Coronavirus Aid, Relief, and Economic Security (CARES) Act was passed in 2020, the FDA was in the middle of amending a sunscreen monograph through the previous rule-making process, and the agency had issued a proposed rule for sunscreens in February of 2019. The CARES Act provided the FDA with new authority related to OTC drugs including sunscreens.

It also established a deemed final order for sunscreens, which set the current requirements for OTC sunscreen products marketed without an application. The deemed final order, released on Sept. 24, “essentially preserves the pre-CARES Act status quo marketing conditions for these sunscreens,” Dr. Michele explained. “Before the CARES Act was passed, sunscreens were marketed according to nearly identical terms that were described in an FDA enforcement discretion policy. For this reason, the agency believes that most sunscreens on the market today are already in compliance with this order.”

The CARES Act also required the FDA to issue a proposed order by Sept. 27 to amend and revise the deemed final order. Dr. Michele described the proposed order, which was released on Sept. 24, as “a vehicle to effectively transition our ongoing consideration of the appropriate requirements for OTC sunscreens marketed without approved applications from the previous rule-making process to this new order process. The provisions in today’s proposed order are therefore substantively the same as those described in the FDA’s 2019 proposed rule on sunscreens. With this proposed order, we’re proposing new requirements to improve the quality, safety, and efficacy of sunscreens that Americans use every day.”

The order proposes to update the generally recognized as safe (GRASE) status for the 16 active ingredients listed in the deemed final order. It also proposes that dosage forms that are GRASE for use as sunscreens include oils, lotions, creams, gels, butters, pastes, ointments, and sticks, and proposes GRASE status for spray sunscreens, subject to testing and labeling requirements.

Adam Friedman, MD, FAAD, professor and chair of dermatology at George Washington University, Washington, emphasized that photoprotection “is important for everyone, regardless of skin tone,” in an interview. “Broad-spectrum sunscreens with an SPF of 15 and higher play an important role in this. This should not be lost amidst the proposed order.”

Changes between the deemed and proposed order that he highlighted include a maximum SPF of 60+ (though up to 80 might be allowed) and that zinc oxide and titanium dioxide are GRASE. “The FDA did not say that nanoparticle formulations of these, which are easier to use, are not GRASE; they are asking for community input,” he said.

Other changes between the deemed and proposed order are that PABA and trolamine salicylate are not GRASE and that broad-spectrum testing will be mandatory. In addition, Dr. Friedman said, “sprays will be considered for GRASE so long as properly tested, labeling should be clearer (and a warning will be applied to those sunscreens not shown to prevent all the bad stuff with UVR [ultraviolet radiation]), and bug spray–sunscreen combos are a no-go.”

The FDA will consider comments on the proposed order submitted during a 45-day public comment period before issuing a revised final order. “As part of this process, we’ll consider all timely comments submitted both in response to the February 2019 proposed rule and to the current proposed order,” Dr. Michele said.

Dr. Friedman reported that he serves as a consultant and/or advisor to numerous pharmaceutical companies. He is also a speaker for Regeneron, Sanofi Genzyme, Abbvie, LRP, Janssen, Incyte, and Brickell Biotech, and has received grants from Pfizer, the Dermatology Foundation, Almirall, Incyte, Galderma, and Janssen.

[email protected]

Federal efforts to improve the quality, safety, and efficacy of over-the-counter sunscreens took a step forward today with the release of two orders aimed at updating regulatory requirements for most sunscreen products in the United States.

“We see it as a key public health priority and our regulatory obligation to make sure that marketed sunscreen products offer protection from the sun’s effects and that they deliver on those promises to consumers,” Theresa Michele, MD, director of the office of nonprescription drugs in the FDA’s Center for Drug Evaluation and Research, said during a media briefing.

When the Coronavirus Aid, Relief, and Economic Security (CARES) Act was passed in 2020, the FDA was in the middle of amending a sunscreen monograph through the previous rule-making process, and the agency had issued a proposed rule for sunscreens in February of 2019. The CARES Act provided the FDA with new authority related to OTC drugs including sunscreens.

It also established a deemed final order for sunscreens, which set the current requirements for OTC sunscreen products marketed without an application. The deemed final order, released on Sept. 24, “essentially preserves the pre-CARES Act status quo marketing conditions for these sunscreens,” Dr. Michele explained. “Before the CARES Act was passed, sunscreens were marketed according to nearly identical terms that were described in an FDA enforcement discretion policy. For this reason, the agency believes that most sunscreens on the market today are already in compliance with this order.”

The CARES Act also required the FDA to issue a proposed order by Sept. 27 to amend and revise the deemed final order. Dr. Michele described the proposed order, which was released on Sept. 24, as “a vehicle to effectively transition our ongoing consideration of the appropriate requirements for OTC sunscreens marketed without approved applications from the previous rule-making process to this new order process. The provisions in today’s proposed order are therefore substantively the same as those described in the FDA’s 2019 proposed rule on sunscreens. With this proposed order, we’re proposing new requirements to improve the quality, safety, and efficacy of sunscreens that Americans use every day.”

The order proposes to update the generally recognized as safe (GRASE) status for the 16 active ingredients listed in the deemed final order. It also proposes that dosage forms that are GRASE for use as sunscreens include oils, lotions, creams, gels, butters, pastes, ointments, and sticks, and proposes GRASE status for spray sunscreens, subject to testing and labeling requirements.

Adam Friedman, MD, FAAD, professor and chair of dermatology at George Washington University, Washington, emphasized that photoprotection “is important for everyone, regardless of skin tone,” in an interview. “Broad-spectrum sunscreens with an SPF of 15 and higher play an important role in this. This should not be lost amidst the proposed order.”

Changes between the deemed and proposed order that he highlighted include a maximum SPF of 60+ (though up to 80 might be allowed) and that zinc oxide and titanium dioxide are GRASE. “The FDA did not say that nanoparticle formulations of these, which are easier to use, are not GRASE; they are asking for community input,” he said.

Other changes between the deemed and proposed order are that PABA and trolamine salicylate are not GRASE and that broad-spectrum testing will be mandatory. In addition, Dr. Friedman said, “sprays will be considered for GRASE so long as properly tested, labeling should be clearer (and a warning will be applied to those sunscreens not shown to prevent all the bad stuff with UVR [ultraviolet radiation]), and bug spray–sunscreen combos are a no-go.”

The FDA will consider comments on the proposed order submitted during a 45-day public comment period before issuing a revised final order. “As part of this process, we’ll consider all timely comments submitted both in response to the February 2019 proposed rule and to the current proposed order,” Dr. Michele said.

Dr. Friedman reported that he serves as a consultant and/or advisor to numerous pharmaceutical companies. He is also a speaker for Regeneron, Sanofi Genzyme, Abbvie, LRP, Janssen, Incyte, and Brickell Biotech, and has received grants from Pfizer, the Dermatology Foundation, Almirall, Incyte, Galderma, and Janssen.

[email protected]

Federal efforts to improve the quality, safety, and efficacy of over-the-counter sunscreens took a step forward today with the release of two orders aimed at updating regulatory requirements for most sunscreen products in the United States.

“We see it as a key public health priority and our regulatory obligation to make sure that marketed sunscreen products offer protection from the sun’s effects and that they deliver on those promises to consumers,” Theresa Michele, MD, director of the office of nonprescription drugs in the FDA’s Center for Drug Evaluation and Research, said during a media briefing.

When the Coronavirus Aid, Relief, and Economic Security (CARES) Act was passed in 2020, the FDA was in the middle of amending a sunscreen monograph through the previous rule-making process, and the agency had issued a proposed rule for sunscreens in February of 2019. The CARES Act provided the FDA with new authority related to OTC drugs including sunscreens.

It also established a deemed final order for sunscreens, which set the current requirements for OTC sunscreen products marketed without an application. The deemed final order, released on Sept. 24, “essentially preserves the pre-CARES Act status quo marketing conditions for these sunscreens,” Dr. Michele explained. “Before the CARES Act was passed, sunscreens were marketed according to nearly identical terms that were described in an FDA enforcement discretion policy. For this reason, the agency believes that most sunscreens on the market today are already in compliance with this order.”

The CARES Act also required the FDA to issue a proposed order by Sept. 27 to amend and revise the deemed final order. Dr. Michele described the proposed order, which was released on Sept. 24, as “a vehicle to effectively transition our ongoing consideration of the appropriate requirements for OTC sunscreens marketed without approved applications from the previous rule-making process to this new order process. The provisions in today’s proposed order are therefore substantively the same as those described in the FDA’s 2019 proposed rule on sunscreens. With this proposed order, we’re proposing new requirements to improve the quality, safety, and efficacy of sunscreens that Americans use every day.”

The order proposes to update the generally recognized as safe (GRASE) status for the 16 active ingredients listed in the deemed final order. It also proposes that dosage forms that are GRASE for use as sunscreens include oils, lotions, creams, gels, butters, pastes, ointments, and sticks, and proposes GRASE status for spray sunscreens, subject to testing and labeling requirements.

Adam Friedman, MD, FAAD, professor and chair of dermatology at George Washington University, Washington, emphasized that photoprotection “is important for everyone, regardless of skin tone,” in an interview. “Broad-spectrum sunscreens with an SPF of 15 and higher play an important role in this. This should not be lost amidst the proposed order.”

Changes between the deemed and proposed order that he highlighted include a maximum SPF of 60+ (though up to 80 might be allowed) and that zinc oxide and titanium dioxide are GRASE. “The FDA did not say that nanoparticle formulations of these, which are easier to use, are not GRASE; they are asking for community input,” he said.

Other changes between the deemed and proposed order are that PABA and trolamine salicylate are not GRASE and that broad-spectrum testing will be mandatory. In addition, Dr. Friedman said, “sprays will be considered for GRASE so long as properly tested, labeling should be clearer (and a warning will be applied to those sunscreens not shown to prevent all the bad stuff with UVR [ultraviolet radiation]), and bug spray–sunscreen combos are a no-go.”

The FDA will consider comments on the proposed order submitted during a 45-day public comment period before issuing a revised final order. “As part of this process, we’ll consider all timely comments submitted both in response to the February 2019 proposed rule and to the current proposed order,” Dr. Michele said.

Dr. Friedman reported that he serves as a consultant and/or advisor to numerous pharmaceutical companies. He is also a speaker for Regeneron, Sanofi Genzyme, Abbvie, LRP, Janssen, Incyte, and Brickell Biotech, and has received grants from Pfizer, the Dermatology Foundation, Almirall, Incyte, Galderma, and Janssen.

[email protected]

Two new cases of a mysterious virus have been reported by the Alaska Department of Health and Social Services. Both people were diagnosed after receiving urgent care in a Fairbanks-area clinic. One was a child with a sore on the left elbow, along with fever and swollen lymph nodes. And the other was an unrelated middle-aged woman with a pox mark on her leg, swollen lymph nodes, and joint pain. In both cases, symptoms improved within 3 weeks.

This isn’t the first time the so-called Alaskapox virus has been detected in the region. In 2015, a woman living near Fairbanks turned up at her doctor’s office with a single reddened pox-like mark on her upper arm and a feeling of fatigue.

Sampling of the pox mark showed that it was caused by a previously unidentified virus of the same family as smallpox and cowpox.

Five years later, another woman showed up with similar signs and symptoms, and her pox also proved to be the result of what public health experts started calling the Alaskapox virus.

In both cases, the women recovered completely.
 

Smallpox-like illness

Public health sleuths figured out that in three of the four cases, the patients lived in a home with a cat or cats, and one of these cats was known to hunt small animals.

Experts already knew that cats mingling in cow pastures and sickened by cattle virus had helped cowpox make the leap from bovines to humans. And just as in the case of cowpox, they suspected that cats might again be spreading this new virus to people, too.

All four of the infected people lived in sparsely populated areas amid forests. Officials laid animal traps where some of the affected people lived and identified the virus in several species of small wild animals.

The animals that turned up most often with Alaskapox were small mouse-like voles. The rodents with rounded muzzles are known for burrowing in the region. And scientists suspect the Alaskapox virus makes its way from these wild animals to humans through their pet cats or possibly by direct exposure outdoors.

None of the four people identified so far with Alaskapox knew each other or interacted, so officials also suspect that there are more cases going unrecognized, possibly because the symptoms are mild or nonexistent.

There are no documented cases of person-to-person transmission of Alaskapox, according to public health officials monitoring the small number of cases. But other pox viruses can spread by direct contact with skin lesions, so clinicians are recommending that people cover wounds with bandages. Three of the people with Alaskapox mistook their lesions at first for a bite from a spider or insect.

A version of this article first appeared on WebMD.com.

Two new cases of a mysterious virus have been reported by the Alaska Department of Health and Social Services. Both people were diagnosed after receiving urgent care in a Fairbanks-area clinic. One was a child with a sore on the left elbow, along with fever and swollen lymph nodes. And the other was an unrelated middle-aged woman with a pox mark on her leg, swollen lymph nodes, and joint pain. In both cases, symptoms improved within 3 weeks.

This isn’t the first time the so-called Alaskapox virus has been detected in the region. In 2015, a woman living near Fairbanks turned up at her doctor’s office with a single reddened pox-like mark on her upper arm and a feeling of fatigue.

Sampling of the pox mark showed that it was caused by a previously unidentified virus of the same family as smallpox and cowpox.

Five years later, another woman showed up with similar signs and symptoms, and her pox also proved to be the result of what public health experts started calling the Alaskapox virus.

In both cases, the women recovered completely.
 

Smallpox-like illness

Public health sleuths figured out that in three of the four cases, the patients lived in a home with a cat or cats, and one of these cats was known to hunt small animals.

Experts already knew that cats mingling in cow pastures and sickened by cattle virus had helped cowpox make the leap from bovines to humans. And just as in the case of cowpox, they suspected that cats might again be spreading this new virus to people, too.

All four of the infected people lived in sparsely populated areas amid forests. Officials laid animal traps where some of the affected people lived and identified the virus in several species of small wild animals.

The animals that turned up most often with Alaskapox were small mouse-like voles. The rodents with rounded muzzles are known for burrowing in the region. And scientists suspect the Alaskapox virus makes its way from these wild animals to humans through their pet cats or possibly by direct exposure outdoors.

None of the four people identified so far with Alaskapox knew each other or interacted, so officials also suspect that there are more cases going unrecognized, possibly because the symptoms are mild or nonexistent.

There are no documented cases of person-to-person transmission of Alaskapox, according to public health officials monitoring the small number of cases. But other pox viruses can spread by direct contact with skin lesions, so clinicians are recommending that people cover wounds with bandages. Three of the people with Alaskapox mistook their lesions at first for a bite from a spider or insect.

A version of this article first appeared on WebMD.com.

Two new cases of a mysterious virus have been reported by the Alaska Department of Health and Social Services. Both people were diagnosed after receiving urgent care in a Fairbanks-area clinic. One was a child with a sore on the left elbow, along with fever and swollen lymph nodes. And the other was an unrelated middle-aged woman with a pox mark on her leg, swollen lymph nodes, and joint pain. In both cases, symptoms improved within 3 weeks.

This isn’t the first time the so-called Alaskapox virus has been detected in the region. In 2015, a woman living near Fairbanks turned up at her doctor’s office with a single reddened pox-like mark on her upper arm and a feeling of fatigue.

Sampling of the pox mark showed that it was caused by a previously unidentified virus of the same family as smallpox and cowpox.

Five years later, another woman showed up with similar signs and symptoms, and her pox also proved to be the result of what public health experts started calling the Alaskapox virus.

In both cases, the women recovered completely.
 

Smallpox-like illness

Public health sleuths figured out that in three of the four cases, the patients lived in a home with a cat or cats, and one of these cats was known to hunt small animals.

Experts already knew that cats mingling in cow pastures and sickened by cattle virus had helped cowpox make the leap from bovines to humans. And just as in the case of cowpox, they suspected that cats might again be spreading this new virus to people, too.

All four of the infected people lived in sparsely populated areas amid forests. Officials laid animal traps where some of the affected people lived and identified the virus in several species of small wild animals.

The animals that turned up most often with Alaskapox were small mouse-like voles. The rodents with rounded muzzles are known for burrowing in the region. And scientists suspect the Alaskapox virus makes its way from these wild animals to humans through their pet cats or possibly by direct exposure outdoors.

None of the four people identified so far with Alaskapox knew each other or interacted, so officials also suspect that there are more cases going unrecognized, possibly because the symptoms are mild or nonexistent.

There are no documented cases of person-to-person transmission of Alaskapox, according to public health officials monitoring the small number of cases. But other pox viruses can spread by direct contact with skin lesions, so clinicians are recommending that people cover wounds with bandages. Three of the people with Alaskapox mistook their lesions at first for a bite from a spider or insect.

A version of this article first appeared on WebMD.com.

Withholding mycophenolate around the time of vaccination against SARS-CoV-2 proved safe and augmented the humoral response to vaccination among a group of patients at one center who were taking the immunosuppressive drug for a variety of rheumatic and musculoskeletal diseases (RMDs).

Previous studies have shown that use of mycophenolate attenuates the humoral response to SARS-CoV-2 vaccination, and the most up-to-date recommendations from the American College of Rheumatology on SARS-CoV-2 vaccination in patients with RMDs advise that mycophenolate should be withheld for a week after receiving the vaccine.

To understand better how withholding mycophenolate would affect immune response to SARS-CoV-2 vaccination, rheumatology fellow Caoilfhionn M. Connolly, MD, and coauthors at Johns Hopkins University, Baltimore, described in their report – published online Sept. 23, 2021, in Annals of the Rheumatic Diseases – how they compared the immune responses to vaccination in 24 patients who withheld mycophenolate and 171 patients who did not stop taking it. All but 1 of the 24 patients who withheld mycophenolate were female, with a median age of 51 years, and they had mostly systemic lupus erythematosus (6 patients), myositis (5), scleroderma (4), or overlap connective tissue disease (4). Three patients received the Janssen/Johnson & Johnson vaccine; all others received either the two-dose Moderna or Pfizer/BioNTech mRNA series.

At a median of 32 days after vaccination, all but two of the patients (92%) who withheld mycophenolate had detectable antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, compared with 65% of those who continued the drug (P = .01). This calculated to patients who withheld the drug as having nearly sixfold higher odds for a positive antibody response (odds ratio, 5.8; 95% CI, 1.3-25.5; P = .02). The association remained statistically significant in an logistic regression analysis that was adjusted for age, sex, race, vaccine type, and use of rituximab and glucocorticoids.

The withholding group also had significantly higher median anti-RBD immunoglobulin titers than did the group that continued therapy (125 vs. 7 U/L; P = .004).

Two patients who reported a flare of their underlying disease during the perivaccination period were treated with topical and oral glucocorticoids.

The patients who withdrew mycophenolate had taken it with twice daily dosing at a median total daily dose of 2,000 mg. They ended up withholding a median of 20 doses around the time of vaccination, with 54% withholding before, 38% both before and after, and 8% only after vaccination.

The researchers said that the conclusions that can be drawn from the study were limited by its small sample size, which “did not allow for evaluation of optimal duration of withholding therapy,” and also its “nonrandomized design, lack of data on cellular response, and limited information on dosing of other immunosuppressive agents.”

Three of the authors disclosed receiving consulting and speaking honoraria from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallincrodt, and Thermo Fisher Scientific. A fourth author has received consulting fees from Janssen, Boehringer Ingelheim, Mallinckrodt, EMD Serono, Allogene, and ArgenX.

[email protected]

Withholding mycophenolate around the time of vaccination against SARS-CoV-2 proved safe and augmented the humoral response to vaccination among a group of patients at one center who were taking the immunosuppressive drug for a variety of rheumatic and musculoskeletal diseases (RMDs).

Previous studies have shown that use of mycophenolate attenuates the humoral response to SARS-CoV-2 vaccination, and the most up-to-date recommendations from the American College of Rheumatology on SARS-CoV-2 vaccination in patients with RMDs advise that mycophenolate should be withheld for a week after receiving the vaccine.

To understand better how withholding mycophenolate would affect immune response to SARS-CoV-2 vaccination, rheumatology fellow Caoilfhionn M. Connolly, MD, and coauthors at Johns Hopkins University, Baltimore, described in their report – published online Sept. 23, 2021, in Annals of the Rheumatic Diseases – how they compared the immune responses to vaccination in 24 patients who withheld mycophenolate and 171 patients who did not stop taking it. All but 1 of the 24 patients who withheld mycophenolate were female, with a median age of 51 years, and they had mostly systemic lupus erythematosus (6 patients), myositis (5), scleroderma (4), or overlap connective tissue disease (4). Three patients received the Janssen/Johnson & Johnson vaccine; all others received either the two-dose Moderna or Pfizer/BioNTech mRNA series.

At a median of 32 days after vaccination, all but two of the patients (92%) who withheld mycophenolate had detectable antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, compared with 65% of those who continued the drug (P = .01). This calculated to patients who withheld the drug as having nearly sixfold higher odds for a positive antibody response (odds ratio, 5.8; 95% CI, 1.3-25.5; P = .02). The association remained statistically significant in an logistic regression analysis that was adjusted for age, sex, race, vaccine type, and use of rituximab and glucocorticoids.

The withholding group also had significantly higher median anti-RBD immunoglobulin titers than did the group that continued therapy (125 vs. 7 U/L; P = .004).

Two patients who reported a flare of their underlying disease during the perivaccination period were treated with topical and oral glucocorticoids.

The patients who withdrew mycophenolate had taken it with twice daily dosing at a median total daily dose of 2,000 mg. They ended up withholding a median of 20 doses around the time of vaccination, with 54% withholding before, 38% both before and after, and 8% only after vaccination.

The researchers said that the conclusions that can be drawn from the study were limited by its small sample size, which “did not allow for evaluation of optimal duration of withholding therapy,” and also its “nonrandomized design, lack of data on cellular response, and limited information on dosing of other immunosuppressive agents.”

Three of the authors disclosed receiving consulting and speaking honoraria from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallincrodt, and Thermo Fisher Scientific. A fourth author has received consulting fees from Janssen, Boehringer Ingelheim, Mallinckrodt, EMD Serono, Allogene, and ArgenX.

[email protected]

Withholding mycophenolate around the time of vaccination against SARS-CoV-2 proved safe and augmented the humoral response to vaccination among a group of patients at one center who were taking the immunosuppressive drug for a variety of rheumatic and musculoskeletal diseases (RMDs).

Previous studies have shown that use of mycophenolate attenuates the humoral response to SARS-CoV-2 vaccination, and the most up-to-date recommendations from the American College of Rheumatology on SARS-CoV-2 vaccination in patients with RMDs advise that mycophenolate should be withheld for a week after receiving the vaccine.

To understand better how withholding mycophenolate would affect immune response to SARS-CoV-2 vaccination, rheumatology fellow Caoilfhionn M. Connolly, MD, and coauthors at Johns Hopkins University, Baltimore, described in their report – published online Sept. 23, 2021, in Annals of the Rheumatic Diseases – how they compared the immune responses to vaccination in 24 patients who withheld mycophenolate and 171 patients who did not stop taking it. All but 1 of the 24 patients who withheld mycophenolate were female, with a median age of 51 years, and they had mostly systemic lupus erythematosus (6 patients), myositis (5), scleroderma (4), or overlap connective tissue disease (4). Three patients received the Janssen/Johnson & Johnson vaccine; all others received either the two-dose Moderna or Pfizer/BioNTech mRNA series.

At a median of 32 days after vaccination, all but two of the patients (92%) who withheld mycophenolate had detectable antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, compared with 65% of those who continued the drug (P = .01). This calculated to patients who withheld the drug as having nearly sixfold higher odds for a positive antibody response (odds ratio, 5.8; 95% CI, 1.3-25.5; P = .02). The association remained statistically significant in an logistic regression analysis that was adjusted for age, sex, race, vaccine type, and use of rituximab and glucocorticoids.

The withholding group also had significantly higher median anti-RBD immunoglobulin titers than did the group that continued therapy (125 vs. 7 U/L; P = .004).

Two patients who reported a flare of their underlying disease during the perivaccination period were treated with topical and oral glucocorticoids.

The patients who withdrew mycophenolate had taken it with twice daily dosing at a median total daily dose of 2,000 mg. They ended up withholding a median of 20 doses around the time of vaccination, with 54% withholding before, 38% both before and after, and 8% only after vaccination.

The researchers said that the conclusions that can be drawn from the study were limited by its small sample size, which “did not allow for evaluation of optimal duration of withholding therapy,” and also its “nonrandomized design, lack of data on cellular response, and limited information on dosing of other immunosuppressive agents.”

Three of the authors disclosed receiving consulting and speaking honoraria from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallincrodt, and Thermo Fisher Scientific. A fourth author has received consulting fees from Janssen, Boehringer Ingelheim, Mallinckrodt, EMD Serono, Allogene, and ArgenX.

[email protected]

The director of the Centers for Disease Control and Prevention late Thursday overruled the recommendation of the agency’s advisory panel to broaden the number of Americans who are now eligible for a third dose of the Pfizer COVID-19 vaccine.

The CDC’s Advisory Committee on Immunization Practices earlier Thursday voted to allow several groups of Americans to get a booster shot, but voted not to recommend it for adults age 18 to 64 who live or work in a place where the risk of COVID-19 is high. That would have included health care workers and other frontline employees.

But CDC Director Rochelle Walensky, MD, decided to reverse that recommendation and include the 18-to-64-year-olds in her final decision.

“As CDC Director, it is my job to recognize where our actions can have the greatest impact,” Dr. Walensky said in a statement late Thursday night, according to published reports. “At CDC, we are tasked with analyzing complex, often imperfect data to make concrete recommendations that optimize health. In a pandemic, even with uncertainty, we must take actions that we anticipate will do the greatest good.”

Dr. Walensky agreed with the rest of the advisory committee's decisions, which included recommendations that the following groups also be eligible for a booster shot:

• Adults ages 65 and up and residents of long-term care facilities
• Adults ages 50 to 64 who have an underlying medical condition that may increase their risk from a COVID infection
• Adults ages 18 to 49 who may be at increased risk from a COVID-19 infection because of an underlying medical condition, if a person feels like they need one based on a consideration of their individual benefit and risks.

About 26 million Americans are at least 6 months past the last dose of the Pfizer vaccines, making them eligible to receive a third dose.  About 13.6 million of them are over the age of 65.  Another 5.3 million are ages 50 to 64.

In making the recommendations, the committee left out healthcare workers. This was a departure from the Food and Drug Administration’s authorization which included boosters for those 65 and over, and for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers – such as those in healthcare -- whose jobs increase their risk for infection.

This is the group Dr. Walensky added to the eligible list on her own.

Committee members “did not buy the need in occupational or institutional settings,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville.  Dr. Schaffner sits on the ACIP workgroup that considered the evidence behind boosters. He said that he would have voted yes to offer boosters to healthcare and other essential workers.

“There was a real split in the committee,” he said.

The vote on boosters for healthcare and other high-risk workers was rejected 9 to 6.

“I think that there is ample evidence that people such as healthcare workers do not have repeated exposure in the workplace,” said Beth Bell, MD, a clinical professor at the University of Washington. “They’re using PPE as they should and they’re following the other policies within the healthcare setting. There’s lots of evidence that suggest that health care workers who become infected become infected because of exposures in the community.”

She was not alone in feeling cautious.

“I think this is an extremely slippery slope,” said Sarah Long, MD, a pediatric infectious disease specialist at Drexel University in Philadelphia, before her vote to reject boosters for healthcare and other high-risk workers.

“We might as well just say, ‘Give it to everybody 18 and over.’ We have an extremely effective vaccine. It’s like saying it’s not working, and it is working.”

The committee saw data showing that all of the vaccines remain highly protective against hospitalization and death for all age groups, though protection against getting sick with COVID has waned slightly over time and with the dominance of the more contagious Delta variant. Those at highest risk for a severe breakthrough infection — those that cause hospitalization or death — are older adults.
 

How much will the U.S. benefit from boosters?

Some felt squeamish about broadly recommending boosters at all.

“We have too much hope on the line with these boosters,” said James Loehr, MD, who is a family physician in Ithaca, N.Y. Dr. Loehr said he felt the goal of giving boosters in the United States should be to decrease hospitalizations, and he felt they would, but that the impact would likely be smaller than appreciated.

Based on his calculations of the benefits of boosters for each age group, Dr. Loehr said if boosters were given to all 13 million seniors previously vaccinated with the Pfizer vaccine, we might prevent 200 hospitalizations a day, “which would be a lot,” he noted. But, he said, “considering that we have 10,000 hospitalizations a day now, it’s probably not that much.”

Others agreed.

“I really think this is a solution looking for a problem,” said Jason Goldman, MD, an associate professor at Florida Atlantic University who was representing the American College of Physicians. “You know, I don’t think it’s going to address the issue of the pandemic. I really think it’s just going to create more confusion on the provider from the position of implementation, and I really think it’s going really far afield of the data.”

ACIP Chair Grace Lee, MD, a pediatric infectious disease specialist at Stanford, said she had cared for children who had died of COVID.

“I can tell you that their family members really wished they had extra protection for their kids, because they weren’t symptomatic. Nobody else was sick at home,” she said.

Dr. Lee said for her, access was paramount, and she was in favor of expanding access to boosters for as many people as possible.
 

Next steps

People who were initially vaccinated with either Moderna or Johnson & Johnson vaccines are excluded from booster recommendations, something many on the committee were uncomfortable with.

The FDA is still considering Moderna’s application to market booster doses. Johnson & Johnson hasn’t yet applied to the FDA for permission to offer second doses in the United States.

While the ACIP’s recommendations are important, in this case, they may not have a huge practical effect, said Schaffner. The CDC has already approved third shots for people who are immunocompromised, and no proof of a medical condition is required to get one.

More than 2 million people have already gotten a third dose, he noted, and not all of them are immunocompromised.

“They have heard the president say that, you know, everybody should get a booster, and they’ve taken that at face value,” he said.

A version of this article first appeared on WebMD.com.

The director of the Centers for Disease Control and Prevention late Thursday overruled the recommendation of the agency’s advisory panel to broaden the number of Americans who are now eligible for a third dose of the Pfizer COVID-19 vaccine.

The CDC’s Advisory Committee on Immunization Practices earlier Thursday voted to allow several groups of Americans to get a booster shot, but voted not to recommend it for adults age 18 to 64 who live or work in a place where the risk of COVID-19 is high. That would have included health care workers and other frontline employees.

But CDC Director Rochelle Walensky, MD, decided to reverse that recommendation and include the 18-to-64-year-olds in her final decision.

“As CDC Director, it is my job to recognize where our actions can have the greatest impact,” Dr. Walensky said in a statement late Thursday night, according to published reports. “At CDC, we are tasked with analyzing complex, often imperfect data to make concrete recommendations that optimize health. In a pandemic, even with uncertainty, we must take actions that we anticipate will do the greatest good.”

Dr. Walensky agreed with the rest of the advisory committee's decisions, which included recommendations that the following groups also be eligible for a booster shot:

• Adults ages 65 and up and residents of long-term care facilities
• Adults ages 50 to 64 who have an underlying medical condition that may increase their risk from a COVID infection
• Adults ages 18 to 49 who may be at increased risk from a COVID-19 infection because of an underlying medical condition, if a person feels like they need one based on a consideration of their individual benefit and risks.

About 26 million Americans are at least 6 months past the last dose of the Pfizer vaccines, making them eligible to receive a third dose.  About 13.6 million of them are over the age of 65.  Another 5.3 million are ages 50 to 64.

In making the recommendations, the committee left out healthcare workers. This was a departure from the Food and Drug Administration’s authorization which included boosters for those 65 and over, and for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers – such as those in healthcare -- whose jobs increase their risk for infection.

This is the group Dr. Walensky added to the eligible list on her own.

Committee members “did not buy the need in occupational or institutional settings,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville.  Dr. Schaffner sits on the ACIP workgroup that considered the evidence behind boosters. He said that he would have voted yes to offer boosters to healthcare and other essential workers.

“There was a real split in the committee,” he said.

The vote on boosters for healthcare and other high-risk workers was rejected 9 to 6.

“I think that there is ample evidence that people such as healthcare workers do not have repeated exposure in the workplace,” said Beth Bell, MD, a clinical professor at the University of Washington. “They’re using PPE as they should and they’re following the other policies within the healthcare setting. There’s lots of evidence that suggest that health care workers who become infected become infected because of exposures in the community.”

She was not alone in feeling cautious.

“I think this is an extremely slippery slope,” said Sarah Long, MD, a pediatric infectious disease specialist at Drexel University in Philadelphia, before her vote to reject boosters for healthcare and other high-risk workers.

“We might as well just say, ‘Give it to everybody 18 and over.’ We have an extremely effective vaccine. It’s like saying it’s not working, and it is working.”

The committee saw data showing that all of the vaccines remain highly protective against hospitalization and death for all age groups, though protection against getting sick with COVID has waned slightly over time and with the dominance of the more contagious Delta variant. Those at highest risk for a severe breakthrough infection — those that cause hospitalization or death — are older adults.
 

How much will the U.S. benefit from boosters?

Some felt squeamish about broadly recommending boosters at all.

“We have too much hope on the line with these boosters,” said James Loehr, MD, who is a family physician in Ithaca, N.Y. Dr. Loehr said he felt the goal of giving boosters in the United States should be to decrease hospitalizations, and he felt they would, but that the impact would likely be smaller than appreciated.

Based on his calculations of the benefits of boosters for each age group, Dr. Loehr said if boosters were given to all 13 million seniors previously vaccinated with the Pfizer vaccine, we might prevent 200 hospitalizations a day, “which would be a lot,” he noted. But, he said, “considering that we have 10,000 hospitalizations a day now, it’s probably not that much.”

Others agreed.

“I really think this is a solution looking for a problem,” said Jason Goldman, MD, an associate professor at Florida Atlantic University who was representing the American College of Physicians. “You know, I don’t think it’s going to address the issue of the pandemic. I really think it’s just going to create more confusion on the provider from the position of implementation, and I really think it’s going really far afield of the data.”

ACIP Chair Grace Lee, MD, a pediatric infectious disease specialist at Stanford, said she had cared for children who had died of COVID.

“I can tell you that their family members really wished they had extra protection for their kids, because they weren’t symptomatic. Nobody else was sick at home,” she said.

Dr. Lee said for her, access was paramount, and she was in favor of expanding access to boosters for as many people as possible.
 

Next steps

People who were initially vaccinated with either Moderna or Johnson & Johnson vaccines are excluded from booster recommendations, something many on the committee were uncomfortable with.

The FDA is still considering Moderna’s application to market booster doses. Johnson & Johnson hasn’t yet applied to the FDA for permission to offer second doses in the United States.

While the ACIP’s recommendations are important, in this case, they may not have a huge practical effect, said Schaffner. The CDC has already approved third shots for people who are immunocompromised, and no proof of a medical condition is required to get one.

More than 2 million people have already gotten a third dose, he noted, and not all of them are immunocompromised.

“They have heard the president say that, you know, everybody should get a booster, and they’ve taken that at face value,” he said.

A version of this article first appeared on WebMD.com.

The director of the Centers for Disease Control and Prevention late Thursday overruled the recommendation of the agency’s advisory panel to broaden the number of Americans who are now eligible for a third dose of the Pfizer COVID-19 vaccine.

The CDC’s Advisory Committee on Immunization Practices earlier Thursday voted to allow several groups of Americans to get a booster shot, but voted not to recommend it for adults age 18 to 64 who live or work in a place where the risk of COVID-19 is high. That would have included health care workers and other frontline employees.

But CDC Director Rochelle Walensky, MD, decided to reverse that recommendation and include the 18-to-64-year-olds in her final decision.

“As CDC Director, it is my job to recognize where our actions can have the greatest impact,” Dr. Walensky said in a statement late Thursday night, according to published reports. “At CDC, we are tasked with analyzing complex, often imperfect data to make concrete recommendations that optimize health. In a pandemic, even with uncertainty, we must take actions that we anticipate will do the greatest good.”

Dr. Walensky agreed with the rest of the advisory committee's decisions, which included recommendations that the following groups also be eligible for a booster shot:

• Adults ages 65 and up and residents of long-term care facilities
• Adults ages 50 to 64 who have an underlying medical condition that may increase their risk from a COVID infection
• Adults ages 18 to 49 who may be at increased risk from a COVID-19 infection because of an underlying medical condition, if a person feels like they need one based on a consideration of their individual benefit and risks.

About 26 million Americans are at least 6 months past the last dose of the Pfizer vaccines, making them eligible to receive a third dose.  About 13.6 million of them are over the age of 65.  Another 5.3 million are ages 50 to 64.

In making the recommendations, the committee left out healthcare workers. This was a departure from the Food and Drug Administration’s authorization which included boosters for those 65 and over, and for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers – such as those in healthcare -- whose jobs increase their risk for infection.

This is the group Dr. Walensky added to the eligible list on her own.

Committee members “did not buy the need in occupational or institutional settings,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville.  Dr. Schaffner sits on the ACIP workgroup that considered the evidence behind boosters. He said that he would have voted yes to offer boosters to healthcare and other essential workers.

“There was a real split in the committee,” he said.

The vote on boosters for healthcare and other high-risk workers was rejected 9 to 6.

“I think that there is ample evidence that people such as healthcare workers do not have repeated exposure in the workplace,” said Beth Bell, MD, a clinical professor at the University of Washington. “They’re using PPE as they should and they’re following the other policies within the healthcare setting. There’s lots of evidence that suggest that health care workers who become infected become infected because of exposures in the community.”

She was not alone in feeling cautious.

“I think this is an extremely slippery slope,” said Sarah Long, MD, a pediatric infectious disease specialist at Drexel University in Philadelphia, before her vote to reject boosters for healthcare and other high-risk workers.

“We might as well just say, ‘Give it to everybody 18 and over.’ We have an extremely effective vaccine. It’s like saying it’s not working, and it is working.”

The committee saw data showing that all of the vaccines remain highly protective against hospitalization and death for all age groups, though protection against getting sick with COVID has waned slightly over time and with the dominance of the more contagious Delta variant. Those at highest risk for a severe breakthrough infection — those that cause hospitalization or death — are older adults.
 

How much will the U.S. benefit from boosters?

Some felt squeamish about broadly recommending boosters at all.

“We have too much hope on the line with these boosters,” said James Loehr, MD, who is a family physician in Ithaca, N.Y. Dr. Loehr said he felt the goal of giving boosters in the United States should be to decrease hospitalizations, and he felt they would, but that the impact would likely be smaller than appreciated.

Based on his calculations of the benefits of boosters for each age group, Dr. Loehr said if boosters were given to all 13 million seniors previously vaccinated with the Pfizer vaccine, we might prevent 200 hospitalizations a day, “which would be a lot,” he noted. But, he said, “considering that we have 10,000 hospitalizations a day now, it’s probably not that much.”

Others agreed.

“I really think this is a solution looking for a problem,” said Jason Goldman, MD, an associate professor at Florida Atlantic University who was representing the American College of Physicians. “You know, I don’t think it’s going to address the issue of the pandemic. I really think it’s just going to create more confusion on the provider from the position of implementation, and I really think it’s going really far afield of the data.”

ACIP Chair Grace Lee, MD, a pediatric infectious disease specialist at Stanford, said she had cared for children who had died of COVID.

“I can tell you that their family members really wished they had extra protection for their kids, because they weren’t symptomatic. Nobody else was sick at home,” she said.

Dr. Lee said for her, access was paramount, and she was in favor of expanding access to boosters for as many people as possible.
 

Next steps

People who were initially vaccinated with either Moderna or Johnson & Johnson vaccines are excluded from booster recommendations, something many on the committee were uncomfortable with.

The FDA is still considering Moderna’s application to market booster doses. Johnson & Johnson hasn’t yet applied to the FDA for permission to offer second doses in the United States.

While the ACIP’s recommendations are important, in this case, they may not have a huge practical effect, said Schaffner. The CDC has already approved third shots for people who are immunocompromised, and no proof of a medical condition is required to get one.

More than 2 million people have already gotten a third dose, he noted, and not all of them are immunocompromised.

“They have heard the president say that, you know, everybody should get a booster, and they’ve taken that at face value,” he said.

A version of this article first appeared on WebMD.com.

Dermatologists may be the first clinicians to diagnose blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare, aggressive hematologic malignancy that involves the skin in about 80% of cases.

Courtesy Dr. Brittney K. DeClerck

“You won’t see blastic plasmacytoid dendritic cell neoplasm listed on our primary cutaneous lymphoma classifications because it’s not technically a primary cutaneous disease,” Brittney K. DeClerck, MD, said during the annual meeting of the Pacific Dermatologic Association. “It’s a systemic disease that has secondary cutaneous manifestations. That’s a very important distinction to make, in terms of not missing the underlying disease associated with what might be commonly first seen on the skin.”

BPDCN is a malignancy of plasmacytoid dendritic cells, which capture, process, and present antigen, and allow the remainder of the immune system to be activated. “They are mainly derived from the myeloid cell lineage, and possibly from the lymphoid line in a subset of cases,” said Dr. DeClerck, associate professor of clinical pathology and dermatology at the University of Southern California, Los Angeles. “They secrete high levels of type I interferons, which is important for antiviral immunity, but they can also be implicated in severe systemic inflammatory diseases, such as systemic lupus erythematosus and systemic sclerosis.”

BPDCN involves the skin in about 80% of cases, she added, “but invariably at some point it involves the bone marrow and has an acute leukemic presentation, whether or not it happens concurrently with what we see on the skin as dermatologists. We also see variable involvement of the peripheral blood, lymph nodes, and the central nervous system.”

The classification of BPDCN has changed over time based on evolving immunohistochemical markers and technologies. For example, in 1995 it was called agranular CD4+ NK cell leukemia, in 2001 it was called blastic NK-cell lymphoma, in 2005 it was called CD4+/CD56+ hematodermic neoplasm, and in 2008 it was called BPDCN (AML subset). In 2016 it became classified as its own entity: BPDCN.

Because of changing nomenclature, the true incidence of the disease is unknown, but according to the best available literature, 75% of cases occur in men and the median age is between 60 and 70 years, “but all ages can be affected,” Dr. DeClerck said. “Cases seem to come in clusters. Our most recent cluster has been in our pediatric population. At Children’s Hospital Los Angeles, we’ve had three cases in the last couple of years. To me, that was a bit unusual.”

She added that 10%-20% of patients will have either a history of, or will develop another, hematologic malignancy, such as myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), or acute myelogenous leukemia (AML).

The general prognosis of BPDCN is poor, and the mean time from onset of lesions to an actual diagnosis is about 6.2 months, which underscores the importance of early diagnosis, Dr. DeClerck said. “There can be some nondescript solitary lesions that patients can present with, so don’t hesitate to biopsy.” The median overall survival is less than 20 months, but patients under 60 years of age have a slightly better prognosis.
 

Clinical presentation

Clinically, the malignancy presents with variable involvement of the skin, bone marrow, lymph nodes, peripheral blood, and central nervous system. “Patients may have one or all of these,” she said. Because 80% of patients have skin lesions, “dermatologists should be aware of this entity in order to communicate with our pathologists to understand that maybe one biopsy isn’t enough. Several biopsies may be required.”

The most common dermatologic presentation of BPDCN is erythematous to deeply violaceous nodules. Other patients may present with infiltrated ecchymotic plaques or petechial to hyperpigmented macules, patches, and plaques. Biopsy reveals a diffusely infiltrated dermis of markedly atypical large cells, but occasionally can be more subtle. “Early lesions may only be perivascular in nature, so going on high power on anything that looks atypical on low power is important in these cases,” Dr. DeClerck said.

The recommended histochemical stains for suspected BPDCN include CD123, CD4, and CD56. “We need to have other stains to rule out other things, such as negative stains that are going to exclude other T cell and B cell processes, and Merkel cell carcinoma, which can express CD56. We also want to have another confirmatory stain because other things can express CD123, CD4, and CD56. Commonly we use TCL1 or TCF4.”

The differential diagnosis of cutaneous findings includes leukemia cutis, mycosis fungoides, NK/T-cell lymphoma, and cutaneous gamma-delta T-cell lymphoma, while the differential diagnosis of biopsy findings includes AML, acute lymphoblastic leukemia, and NK/T-cell lymphoma.

Treatment of BPDCN

Historically, BPDCN was treated with multiagent high-dose chemotherapy. “Patients would frequently respond early but would relapse quickly, progress, and have a poor outcome,” Dr. DeClerck said. Now, first-line therapy is tagraxofusp-erzs (Elzonris) or multiagent chemotherapy based on where the patient is in the course of disease. Tagraxofusp-erzs is an IL-3 conjugated diphtheria toxic fusion protein which binds to CD123, which was approved by the Food and Drug Administration in 2018 for treating BPDCN. After that initial therapy, it is determined whether the patient has a complete response or failed response, she said. “If they have a complete response, they frequently go on to bone marrow transplantation, which is the only curative therapy at this point for these patients.”

According to Dr. DeClerck, an anti-BCL-2 therapy, venetoclax, can be used for patients with BPDCN as well. National Comprehensive Cancer Network (NCCN) guidelines for the treatment of BPDCN can be found on the NCCN website.

Dr. DeClerck emphasized the importance of reviewing biopsy results with a hematopathologist, “because there are complex leukemias that are beyond what dermatopathologists have been trained in.” Once a patient is diagnosed with BPDCN, she recommends rapid referral to a large center for treatment and possible bone marrow transplantation.

Dr. DeClerck disclosed that she is an adviser for tagraxofusp-erzs manufacturer Stemline Therapeutics.

[email protected]

Dermatologists may be the first clinicians to diagnose blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare, aggressive hematologic malignancy that involves the skin in about 80% of cases.

Courtesy Dr. Brittney K. DeClerck

“You won’t see blastic plasmacytoid dendritic cell neoplasm listed on our primary cutaneous lymphoma classifications because it’s not technically a primary cutaneous disease,” Brittney K. DeClerck, MD, said during the annual meeting of the Pacific Dermatologic Association. “It’s a systemic disease that has secondary cutaneous manifestations. That’s a very important distinction to make, in terms of not missing the underlying disease associated with what might be commonly first seen on the skin.”

BPDCN is a malignancy of plasmacytoid dendritic cells, which capture, process, and present antigen, and allow the remainder of the immune system to be activated. “They are mainly derived from the myeloid cell lineage, and possibly from the lymphoid line in a subset of cases,” said Dr. DeClerck, associate professor of clinical pathology and dermatology at the University of Southern California, Los Angeles. “They secrete high levels of type I interferons, which is important for antiviral immunity, but they can also be implicated in severe systemic inflammatory diseases, such as systemic lupus erythematosus and systemic sclerosis.”

BPDCN involves the skin in about 80% of cases, she added, “but invariably at some point it involves the bone marrow and has an acute leukemic presentation, whether or not it happens concurrently with what we see on the skin as dermatologists. We also see variable involvement of the peripheral blood, lymph nodes, and the central nervous system.”

The classification of BPDCN has changed over time based on evolving immunohistochemical markers and technologies. For example, in 1995 it was called agranular CD4+ NK cell leukemia, in 2001 it was called blastic NK-cell lymphoma, in 2005 it was called CD4+/CD56+ hematodermic neoplasm, and in 2008 it was called BPDCN (AML subset). In 2016 it became classified as its own entity: BPDCN.

Because of changing nomenclature, the true incidence of the disease is unknown, but according to the best available literature, 75% of cases occur in men and the median age is between 60 and 70 years, “but all ages can be affected,” Dr. DeClerck said. “Cases seem to come in clusters. Our most recent cluster has been in our pediatric population. At Children’s Hospital Los Angeles, we’ve had three cases in the last couple of years. To me, that was a bit unusual.”

She added that 10%-20% of patients will have either a history of, or will develop another, hematologic malignancy, such as myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), or acute myelogenous leukemia (AML).

The general prognosis of BPDCN is poor, and the mean time from onset of lesions to an actual diagnosis is about 6.2 months, which underscores the importance of early diagnosis, Dr. DeClerck said. “There can be some nondescript solitary lesions that patients can present with, so don’t hesitate to biopsy.” The median overall survival is less than 20 months, but patients under 60 years of age have a slightly better prognosis.
 

Clinical presentation

Clinically, the malignancy presents with variable involvement of the skin, bone marrow, lymph nodes, peripheral blood, and central nervous system. “Patients may have one or all of these,” she said. Because 80% of patients have skin lesions, “dermatologists should be aware of this entity in order to communicate with our pathologists to understand that maybe one biopsy isn’t enough. Several biopsies may be required.”

The most common dermatologic presentation of BPDCN is erythematous to deeply violaceous nodules. Other patients may present with infiltrated ecchymotic plaques or petechial to hyperpigmented macules, patches, and plaques. Biopsy reveals a diffusely infiltrated dermis of markedly atypical large cells, but occasionally can be more subtle. “Early lesions may only be perivascular in nature, so going on high power on anything that looks atypical on low power is important in these cases,” Dr. DeClerck said.

The recommended histochemical stains for suspected BPDCN include CD123, CD4, and CD56. “We need to have other stains to rule out other things, such as negative stains that are going to exclude other T cell and B cell processes, and Merkel cell carcinoma, which can express CD56. We also want to have another confirmatory stain because other things can express CD123, CD4, and CD56. Commonly we use TCL1 or TCF4.”

The differential diagnosis of cutaneous findings includes leukemia cutis, mycosis fungoides, NK/T-cell lymphoma, and cutaneous gamma-delta T-cell lymphoma, while the differential diagnosis of biopsy findings includes AML, acute lymphoblastic leukemia, and NK/T-cell lymphoma.

Treatment of BPDCN

Historically, BPDCN was treated with multiagent high-dose chemotherapy. “Patients would frequently respond early but would relapse quickly, progress, and have a poor outcome,” Dr. DeClerck said. Now, first-line therapy is tagraxofusp-erzs (Elzonris) or multiagent chemotherapy based on where the patient is in the course of disease. Tagraxofusp-erzs is an IL-3 conjugated diphtheria toxic fusion protein which binds to CD123, which was approved by the Food and Drug Administration in 2018 for treating BPDCN. After that initial therapy, it is determined whether the patient has a complete response or failed response, she said. “If they have a complete response, they frequently go on to bone marrow transplantation, which is the only curative therapy at this point for these patients.”

According to Dr. DeClerck, an anti-BCL-2 therapy, venetoclax, can be used for patients with BPDCN as well. National Comprehensive Cancer Network (NCCN) guidelines for the treatment of BPDCN can be found on the NCCN website.

Dr. DeClerck emphasized the importance of reviewing biopsy results with a hematopathologist, “because there are complex leukemias that are beyond what dermatopathologists have been trained in.” Once a patient is diagnosed with BPDCN, she recommends rapid referral to a large center for treatment and possible bone marrow transplantation.

Dr. DeClerck disclosed that she is an adviser for tagraxofusp-erzs manufacturer Stemline Therapeutics.

[email protected]

Dermatologists may be the first clinicians to diagnose blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare, aggressive hematologic malignancy that involves the skin in about 80% of cases.

Courtesy Dr. Brittney K. DeClerck

“You won’t see blastic plasmacytoid dendritic cell neoplasm listed on our primary cutaneous lymphoma classifications because it’s not technically a primary cutaneous disease,” Brittney K. DeClerck, MD, said during the annual meeting of the Pacific Dermatologic Association. “It’s a systemic disease that has secondary cutaneous manifestations. That’s a very important distinction to make, in terms of not missing the underlying disease associated with what might be commonly first seen on the skin.”

BPDCN is a malignancy of plasmacytoid dendritic cells, which capture, process, and present antigen, and allow the remainder of the immune system to be activated. “They are mainly derived from the myeloid cell lineage, and possibly from the lymphoid line in a subset of cases,” said Dr. DeClerck, associate professor of clinical pathology and dermatology at the University of Southern California, Los Angeles. “They secrete high levels of type I interferons, which is important for antiviral immunity, but they can also be implicated in severe systemic inflammatory diseases, such as systemic lupus erythematosus and systemic sclerosis.”

BPDCN involves the skin in about 80% of cases, she added, “but invariably at some point it involves the bone marrow and has an acute leukemic presentation, whether or not it happens concurrently with what we see on the skin as dermatologists. We also see variable involvement of the peripheral blood, lymph nodes, and the central nervous system.”

The classification of BPDCN has changed over time based on evolving immunohistochemical markers and technologies. For example, in 1995 it was called agranular CD4+ NK cell leukemia, in 2001 it was called blastic NK-cell lymphoma, in 2005 it was called CD4+/CD56+ hematodermic neoplasm, and in 2008 it was called BPDCN (AML subset). In 2016 it became classified as its own entity: BPDCN.

Because of changing nomenclature, the true incidence of the disease is unknown, but according to the best available literature, 75% of cases occur in men and the median age is between 60 and 70 years, “but all ages can be affected,” Dr. DeClerck said. “Cases seem to come in clusters. Our most recent cluster has been in our pediatric population. At Children’s Hospital Los Angeles, we’ve had three cases in the last couple of years. To me, that was a bit unusual.”

She added that 10%-20% of patients will have either a history of, or will develop another, hematologic malignancy, such as myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), or acute myelogenous leukemia (AML).

The general prognosis of BPDCN is poor, and the mean time from onset of lesions to an actual diagnosis is about 6.2 months, which underscores the importance of early diagnosis, Dr. DeClerck said. “There can be some nondescript solitary lesions that patients can present with, so don’t hesitate to biopsy.” The median overall survival is less than 20 months, but patients under 60 years of age have a slightly better prognosis.
 

Clinical presentation

Clinically, the malignancy presents with variable involvement of the skin, bone marrow, lymph nodes, peripheral blood, and central nervous system. “Patients may have one or all of these,” she said. Because 80% of patients have skin lesions, “dermatologists should be aware of this entity in order to communicate with our pathologists to understand that maybe one biopsy isn’t enough. Several biopsies may be required.”

The most common dermatologic presentation of BPDCN is erythematous to deeply violaceous nodules. Other patients may present with infiltrated ecchymotic plaques or petechial to hyperpigmented macules, patches, and plaques. Biopsy reveals a diffusely infiltrated dermis of markedly atypical large cells, but occasionally can be more subtle. “Early lesions may only be perivascular in nature, so going on high power on anything that looks atypical on low power is important in these cases,” Dr. DeClerck said.

The recommended histochemical stains for suspected BPDCN include CD123, CD4, and CD56. “We need to have other stains to rule out other things, such as negative stains that are going to exclude other T cell and B cell processes, and Merkel cell carcinoma, which can express CD56. We also want to have another confirmatory stain because other things can express CD123, CD4, and CD56. Commonly we use TCL1 or TCF4.”

The differential diagnosis of cutaneous findings includes leukemia cutis, mycosis fungoides, NK/T-cell lymphoma, and cutaneous gamma-delta T-cell lymphoma, while the differential diagnosis of biopsy findings includes AML, acute lymphoblastic leukemia, and NK/T-cell lymphoma.

Treatment of BPDCN

Historically, BPDCN was treated with multiagent high-dose chemotherapy. “Patients would frequently respond early but would relapse quickly, progress, and have a poor outcome,” Dr. DeClerck said. Now, first-line therapy is tagraxofusp-erzs (Elzonris) or multiagent chemotherapy based on where the patient is in the course of disease. Tagraxofusp-erzs is an IL-3 conjugated diphtheria toxic fusion protein which binds to CD123, which was approved by the Food and Drug Administration in 2018 for treating BPDCN. After that initial therapy, it is determined whether the patient has a complete response or failed response, she said. “If they have a complete response, they frequently go on to bone marrow transplantation, which is the only curative therapy at this point for these patients.”

According to Dr. DeClerck, an anti-BCL-2 therapy, venetoclax, can be used for patients with BPDCN as well. National Comprehensive Cancer Network (NCCN) guidelines for the treatment of BPDCN can be found on the NCCN website.

Dr. DeClerck emphasized the importance of reviewing biopsy results with a hematopathologist, “because there are complex leukemias that are beyond what dermatopathologists have been trained in.” Once a patient is diagnosed with BPDCN, she recommends rapid referral to a large center for treatment and possible bone marrow transplantation.

Dr. DeClerck disclosed that she is an adviser for tagraxofusp-erzs manufacturer Stemline Therapeutics.

[email protected]

A strain of COVID-19 first reported in Japan surfaced at a Kentucky nursing home in the spring.

Deadline, citing a Centers for Disease Control and Prevention report, said 26 residents and 20 workers tested positive for COVID-19 at a skilled care nursing home. The facility has 83 residents and 116 employees.

On March 1, 28 specimens that had been subjected to whole genome sequencing were found to have “mutations aligning with the R.1 lineage,” Deadline said.

About 90% of the facility’s residents and 52% of the staff had received two COVID vaccine doses, the CDC said. Because of the high vaccination rate, the finding raises concerns about “reduced protective immunity” in relation to the R.1 variant, the CDC said.

However, the nursing home case appears to show that the vaccine keeps most people from getting extremely sick, the CDC said. The vaccine was 86.5% protective against symptomatic illness among residents and 87.1% protective for employees.

“Compared with unvaccinated persons, vaccinated persons had reduced risk for SARS-CoV-2 infection and symptomatic COVID-19,” the CDC said. The vaccination of nursing home residents and health care workers “is essential to reduce the risk for symptomatic COVID-19, as is continued focus on infection prevention and control practices,” the CDC said.

Since being reported in Kentucky, R.1 has been detected more than 10,000 times in the United States, Forbes reported, basing that number on entries in the GISAID SARS-CoV-2 database.

Overall, more than 42 million cases of COVID have been reported since the start of the pandemic.

Deadline reported that the R.1 strain was first detected in Japan in January among three members of one family. The family members had no history of traveling abroad, Deadline said, citing an National Institutes of Health report.

The CDC has not classified R.1 as a variant of concern yet but noted it has “several mutations of importance” and “demonstrates evidence of increasing virus transmissibility.”

A version of this article first appeared on WebMD.com.

A strain of COVID-19 first reported in Japan surfaced at a Kentucky nursing home in the spring.

Deadline, citing a Centers for Disease Control and Prevention report, said 26 residents and 20 workers tested positive for COVID-19 at a skilled care nursing home. The facility has 83 residents and 116 employees.

On March 1, 28 specimens that had been subjected to whole genome sequencing were found to have “mutations aligning with the R.1 lineage,” Deadline said.

About 90% of the facility’s residents and 52% of the staff had received two COVID vaccine doses, the CDC said. Because of the high vaccination rate, the finding raises concerns about “reduced protective immunity” in relation to the R.1 variant, the CDC said.

However, the nursing home case appears to show that the vaccine keeps most people from getting extremely sick, the CDC said. The vaccine was 86.5% protective against symptomatic illness among residents and 87.1% protective for employees.

“Compared with unvaccinated persons, vaccinated persons had reduced risk for SARS-CoV-2 infection and symptomatic COVID-19,” the CDC said. The vaccination of nursing home residents and health care workers “is essential to reduce the risk for symptomatic COVID-19, as is continued focus on infection prevention and control practices,” the CDC said.

Since being reported in Kentucky, R.1 has been detected more than 10,000 times in the United States, Forbes reported, basing that number on entries in the GISAID SARS-CoV-2 database.

Overall, more than 42 million cases of COVID have been reported since the start of the pandemic.

Deadline reported that the R.1 strain was first detected in Japan in January among three members of one family. The family members had no history of traveling abroad, Deadline said, citing an National Institutes of Health report.

The CDC has not classified R.1 as a variant of concern yet but noted it has “several mutations of importance” and “demonstrates evidence of increasing virus transmissibility.”

A version of this article first appeared on WebMD.com.

A strain of COVID-19 first reported in Japan surfaced at a Kentucky nursing home in the spring.

Deadline, citing a Centers for Disease Control and Prevention report, said 26 residents and 20 workers tested positive for COVID-19 at a skilled care nursing home. The facility has 83 residents and 116 employees.

On March 1, 28 specimens that had been subjected to whole genome sequencing were found to have “mutations aligning with the R.1 lineage,” Deadline said.

About 90% of the facility’s residents and 52% of the staff had received two COVID vaccine doses, the CDC said. Because of the high vaccination rate, the finding raises concerns about “reduced protective immunity” in relation to the R.1 variant, the CDC said.

However, the nursing home case appears to show that the vaccine keeps most people from getting extremely sick, the CDC said. The vaccine was 86.5% protective against symptomatic illness among residents and 87.1% protective for employees.

“Compared with unvaccinated persons, vaccinated persons had reduced risk for SARS-CoV-2 infection and symptomatic COVID-19,” the CDC said. The vaccination of nursing home residents and health care workers “is essential to reduce the risk for symptomatic COVID-19, as is continued focus on infection prevention and control practices,” the CDC said.

Since being reported in Kentucky, R.1 has been detected more than 10,000 times in the United States, Forbes reported, basing that number on entries in the GISAID SARS-CoV-2 database.

Overall, more than 42 million cases of COVID have been reported since the start of the pandemic.

Deadline reported that the R.1 strain was first detected in Japan in January among three members of one family. The family members had no history of traveling abroad, Deadline said, citing an National Institutes of Health report.

The CDC has not classified R.1 as a variant of concern yet but noted it has “several mutations of importance” and “demonstrates evidence of increasing virus transmissibility.”

A version of this article first appeared on WebMD.com.

Bacteria get the rack ... the towel rack

Obviously, bathrooms have germs. Some people are cleaner about their bathrooms than others, but in general most people just try not to think about the microscopic critters crawling about.

Now you would probably think that the toilet is the dirtiest part of the bathroom because that’s where ... you know, most of the business takes place. Or maybe you’d guess the floor. Truth be told, though, the dirtiest part of the bathroom is where the towels are hung.

pxfuel

Anti-vaxxers would like to be called ‘purebloods’

COVID-19 anti-vaxxers are an interesting bunch, to be kind. And TikTok is a wacky place. So you can just imagine that anti-vaxxer TikTok is a very strange place. The citizens of anti-vax TikTok have decided that the real reason so many people dislike them is branding. They consider anti-vaccination to be a negative word (duh), so they now want to be referred to as “purebloods.”

peterschreiber_media/iStock/Getty Images

Harry Potter doesn’t quite occupy the zeitgeist as it once did, so let’s give you a reminder: In the books, purebloods came from old wizarding families and claimed not to have any Muggle, or nonmagic, blood. While having pure wizard blood was no guarantee of being a villain, most of them were. In addition, it is made quite clear throughout the novels that having supposedly pure blood had no relevance on one’s wizarding ability. Pureblood was a meaningless title, and only the characters with small, cruel minds concerned themselves over it.

Perhaps the anti-vaxxers have decided that they want to be called the same thing. Maybe they just like the name. It does sound impressive and vaguely regal: Pureblood. Like something the nobles of medieval Europe might have used.

Critical-thinking skills may be in short supply here, or maybe the anti-vaxxers know exactly what they’re doing.
 

Hated broccoli? Blame your DNA

Were you that kid who would rather sit at the table for hours than eat your broccoli? Well, as much as your parents might have pushed you, new research suggests that it might be their fault you didn’t like it to begin with.

Hans Braxmeier/Pixabay

Investigators at Australia’s national science agency, CSIRO, recently reported that distaste for Brassica vegetables – broccoli, Brussels sprouts, cabbage, and cauliflower – can be traced to the oral microbiome.

These vegetables have a compound called S-methyl-L-cysteine sulfoxide that gives off sulfurous odors ... mmm, sulfurous ... when mixed with an enzyme in the plant, and that enzyme is also produced by bacteria in some people’s oral microbiomes. So why do adults tolerate these Brassica veggies more than children? It’s all about levels.

The researchers tested the idea by asking 98 child/parent pairs to rate the odors and by using gas chromatography-olfactometry-mass spectrometry to identify the odor-active compounds in both raw and steamed cauliflower and broccoli. The children whose saliva produced high levels of sulfur volatiles disliked Brassica vegetables the most, they reported, and the children with high levels of sulfur volatiles usually had parents who produced high levels.

Despite that connection, however, the distaste for raw Brassica seen in children wasn’t seen in adults.

Maybe it’s not that taste buds change as we age, maybe we just learn to tolerate the sulfurousness.

Bacteria get the rack ... the towel rack

Obviously, bathrooms have germs. Some people are cleaner about their bathrooms than others, but in general most people just try not to think about the microscopic critters crawling about.

Now you would probably think that the toilet is the dirtiest part of the bathroom because that’s where ... you know, most of the business takes place. Or maybe you’d guess the floor. Truth be told, though, the dirtiest part of the bathroom is where the towels are hung.

pxfuel

Anti-vaxxers would like to be called ‘purebloods’

COVID-19 anti-vaxxers are an interesting bunch, to be kind. And TikTok is a wacky place. So you can just imagine that anti-vaxxer TikTok is a very strange place. The citizens of anti-vax TikTok have decided that the real reason so many people dislike them is branding. They consider anti-vaccination to be a negative word (duh), so they now want to be referred to as “purebloods.”

peterschreiber_media/iStock/Getty Images

Harry Potter doesn’t quite occupy the zeitgeist as it once did, so let’s give you a reminder: In the books, purebloods came from old wizarding families and claimed not to have any Muggle, or nonmagic, blood. While having pure wizard blood was no guarantee of being a villain, most of them were. In addition, it is made quite clear throughout the novels that having supposedly pure blood had no relevance on one’s wizarding ability. Pureblood was a meaningless title, and only the characters with small, cruel minds concerned themselves over it.

Perhaps the anti-vaxxers have decided that they want to be called the same thing. Maybe they just like the name. It does sound impressive and vaguely regal: Pureblood. Like something the nobles of medieval Europe might have used.

Critical-thinking skills may be in short supply here, or maybe the anti-vaxxers know exactly what they’re doing.
 

Hated broccoli? Blame your DNA

Were you that kid who would rather sit at the table for hours than eat your broccoli? Well, as much as your parents might have pushed you, new research suggests that it might be their fault you didn’t like it to begin with.

Hans Braxmeier/Pixabay

Investigators at Australia’s national science agency, CSIRO, recently reported that distaste for Brassica vegetables – broccoli, Brussels sprouts, cabbage, and cauliflower – can be traced to the oral microbiome.

These vegetables have a compound called S-methyl-L-cysteine sulfoxide that gives off sulfurous odors ... mmm, sulfurous ... when mixed with an enzyme in the plant, and that enzyme is also produced by bacteria in some people’s oral microbiomes. So why do adults tolerate these Brassica veggies more than children? It’s all about levels.

The researchers tested the idea by asking 98 child/parent pairs to rate the odors and by using gas chromatography-olfactometry-mass spectrometry to identify the odor-active compounds in both raw and steamed cauliflower and broccoli. The children whose saliva produced high levels of sulfur volatiles disliked Brassica vegetables the most, they reported, and the children with high levels of sulfur volatiles usually had parents who produced high levels.

Despite that connection, however, the distaste for raw Brassica seen in children wasn’t seen in adults.

Maybe it’s not that taste buds change as we age, maybe we just learn to tolerate the sulfurousness.

Bacteria get the rack ... the towel rack

Obviously, bathrooms have germs. Some people are cleaner about their bathrooms than others, but in general most people just try not to think about the microscopic critters crawling about.

Now you would probably think that the toilet is the dirtiest part of the bathroom because that’s where ... you know, most of the business takes place. Or maybe you’d guess the floor. Truth be told, though, the dirtiest part of the bathroom is where the towels are hung.

pxfuel

Anti-vaxxers would like to be called ‘purebloods’

COVID-19 anti-vaxxers are an interesting bunch, to be kind. And TikTok is a wacky place. So you can just imagine that anti-vaxxer TikTok is a very strange place. The citizens of anti-vax TikTok have decided that the real reason so many people dislike them is branding. They consider anti-vaccination to be a negative word (duh), so they now want to be referred to as “purebloods.”

peterschreiber_media/iStock/Getty Images

Harry Potter doesn’t quite occupy the zeitgeist as it once did, so let’s give you a reminder: In the books, purebloods came from old wizarding families and claimed not to have any Muggle, or nonmagic, blood. While having pure wizard blood was no guarantee of being a villain, most of them were. In addition, it is made quite clear throughout the novels that having supposedly pure blood had no relevance on one’s wizarding ability. Pureblood was a meaningless title, and only the characters with small, cruel minds concerned themselves over it.

Perhaps the anti-vaxxers have decided that they want to be called the same thing. Maybe they just like the name. It does sound impressive and vaguely regal: Pureblood. Like something the nobles of medieval Europe might have used.

Critical-thinking skills may be in short supply here, or maybe the anti-vaxxers know exactly what they’re doing.
 

Hated broccoli? Blame your DNA

Were you that kid who would rather sit at the table for hours than eat your broccoli? Well, as much as your parents might have pushed you, new research suggests that it might be their fault you didn’t like it to begin with.

Hans Braxmeier/Pixabay

Investigators at Australia’s national science agency, CSIRO, recently reported that distaste for Brassica vegetables – broccoli, Brussels sprouts, cabbage, and cauliflower – can be traced to the oral microbiome.

These vegetables have a compound called S-methyl-L-cysteine sulfoxide that gives off sulfurous odors ... mmm, sulfurous ... when mixed with an enzyme in the plant, and that enzyme is also produced by bacteria in some people’s oral microbiomes. So why do adults tolerate these Brassica veggies more than children? It’s all about levels.

The researchers tested the idea by asking 98 child/parent pairs to rate the odors and by using gas chromatography-olfactometry-mass spectrometry to identify the odor-active compounds in both raw and steamed cauliflower and broccoli. The children whose saliva produced high levels of sulfur volatiles disliked Brassica vegetables the most, they reported, and the children with high levels of sulfur volatiles usually had parents who produced high levels.

Despite that connection, however, the distaste for raw Brassica seen in children wasn’t seen in adults.

Maybe it’s not that taste buds change as we age, maybe we just learn to tolerate the sulfurousness.

The U.S. Food and Drug Administration (FDA) late Sept. 22 granted emergency use authorization (EUA) for a third dose of the Pfizer COVID-19 vaccine for those over the age of 65 and a wide swath of Americans at higher risk for infection.

The agency’s move comes as a Centers for Disease Control and Prevention (CDC) panel ended the first day of a 2-day meeting. That panel, the Advisory Committee on Immunization Practices (ACIP), is expected to vote Sept. 23 to instruct doctors on how to administer the boosters.

The FDA officially authorized the vaccine not only for individuals 65 and older, but also for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers whose jobs increase their risk for infection.

“After considering the totality of the available scientific evidence and the deliberations of our advisory committee of independent, external experts, the FDA amended the EUA for the Pfizer-BioNTech COVID-19 vaccine to allow for a booster dose in certain populations such as health care workers, teachers and daycare staff, grocery workers and those in homeless shelters or prisons, among others,” Acting FDA Commissioner Janet Woodcock, MD, said in a news release.

The recommendations align with those from an FDA advisory panel Sept. 17.

The agency determined that the benefits of a booster dose outweigh the risks for people now authorized to receive it, according to the news release.
 

Other questions remain

So, how will this work? That was the main question weighing on the minds of the CDC’s ACIP during their first day of a 2-day meeting where they are expected to make recommendations on booster doses for Americans.

The panel discussed situations the FDA will still need to consider, such as what should be done for Americans who were originally vaccinated with a Moderna or Johnson and Johnson vaccine, but are not covered under the revised EUA, which is only for those people who received Pfizer’s two-dose vaccine regimen.

“That’s going to leave half of the people immunized in this age group having received the vaccine and being told that they’re at risk now for waning immunity and hospitalization unable to get a booster dose,” said committee member Sarah S. Long, MD, a professor of pediatrics at Drexel University College of Medicine in Philadelphia. “So that’s a big public health panic that we would like to avoid.”

Johnson and Johnson recently reported that second doses of its vaccine boosted its efficacy to almost 94% against COVID-19. A new study, published ahead of peer review, suggests that the efficacy of the single-dose Johnson and Johnson shot has fallen to about 78% against symptomatic infection during the Delta surge.

Moderna has applied for permission to market third doses of its vaccine in the United States, but the FDA has given no timeline on when it might make a decision. 

Doran Fink, MD, PhD, deputy director of the FDA’s Division of Vaccines and Related Products Applications, a representative advising the committee Sept. 22, said the agency was working as rapidly as possible on Moderna’s submission.

Regarding the question of whether it was OK to mix vaccines, rather than match them, Dr. Fink said there are currently not enough data available to inform that decision.

Those answers are coming, though. John Beigel, MD, associate director of clinical research at the National Institute of Allergy and Infectious Diseases, revealed that the federal government has a study underway to see what happens when the vaccines are mixed with each other. 

He said that data from the study would be available later this fall, and would certainly help physicians and other healthcare providers know whether it’s effective or safe to use them interchangeably.
 

Correlates of immunity

The ACIP left much of its schedule open Sept. 23 to discuss extra Pfizer doses and vote on how they should be used.

Pfizer had originally applied to the FDA for an amendment to its FDA approval, which would have given doctors a freer hand to prescribe third doses as they saw fit, in patients as young as 16.

But the FDA’s Vaccines and Related Biological Products Advisory Committee voted Sept. 17 against granting the amendment. The committee was particularly concerned about the lack of data in teens ages 16 and 17, who have the highest risk for a rare side effect that causes heart inflammation that requires hospital care.

Instead, they recommended — and the FDA agreed per their decision Sept. 22 — that third doses should be given to people at higher risk for severe breakthrough infections because of advanced age or because they work in an occupation that puts them at high risk for exposure. 

The CDC panel heard important presentations on new science that is helping to identify the correlates of immunity. 

The correlates of immunity are biomarkers that can be measured in blood that help doctors understand how protected a person may be against COVID-19. These markers of immunity are not yet known for the COVID-19 vaccines.

Emerging evidence shows that booster doses of the Pfizer vaccine cause front-line immune defenders — called binding antibodies — to roughly triple soon after a person gets the third shot. 

Neutralizing antibodies also jump soon after two vaccine doses, but they fall over time, which is natural. The body doesn’t need these foot soldiers to be on guard all the time, so they go away. 

The body retains its memory of how to make them, however, so they can quickly be marshaled again, if needed.

Early studies suggest that antibodies account for about two thirds of a person’s protection against COVID, while the longer-lasting T-cells and B-cells account for about one third.

After the antibody levels fall, it may take a few days to recreate this army. In the meantime, the virus can try to break in. This can cause symptoms, which can make a person feel terrible, but for the most part, vaccinated individuals don’t need hospital care and are nearly always protected from dying — even against the Delta variant.

Those most likely to be at risk for a breakthrough infection are older, because immune function wanes with age.
 

Essential workers

Essential workers, such as those who work in healthcare, may also benefit from high antibody levels, which can minimize symptoms and help them get back to work more quickly.

Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, said that in her area staffing levels are critical right now.

“I’m actually sitting in one of the deepest red [states] with high rates of COVID. We don’t have enough health care workers currently to take care of the unvaccinated,” she said. 

“When we have beds, we are often missing staff, and so the idea of vaccinating health care workers is to be a little bit different than our idea of using vaccines in the general population,” Dr. Talbot said.

Oliver Brooks, MD, chief medical officer of the Watts Healthcare Corporation in Los Angeles, said he was in favor of making a public statement about the temporary nature of the potential recommendations Sept. 23, because they probably won’t cover all who might need a third shot.

“We may want to go on record stating what it is that would allow us to broaden our recommendation or restrict our recommendation,” Dr. Brooks said.

The considerations of who should get an extra dose are not always straightforward.

New modeling by the Harvard TH Chan School of Public Health and the CDC to assist the government’s decisions on boosters had a surprise finding: in nursing homes, it’s more effective to vaccinate healthcare workers than it is to give booster doses to these residents. Nursing homes are at the mercy of community transmission. 

In regions with high transmission, it’s easy for a caregiver to bring the virus into a facility — so the models found that the transmission from these workers is a more effective strategy than giving third doses to the already highly vaccinated group of seniors who live in them.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration (FDA) late Sept. 22 granted emergency use authorization (EUA) for a third dose of the Pfizer COVID-19 vaccine for those over the age of 65 and a wide swath of Americans at higher risk for infection.

The agency’s move comes as a Centers for Disease Control and Prevention (CDC) panel ended the first day of a 2-day meeting. That panel, the Advisory Committee on Immunization Practices (ACIP), is expected to vote Sept. 23 to instruct doctors on how to administer the boosters.

The FDA officially authorized the vaccine not only for individuals 65 and older, but also for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers whose jobs increase their risk for infection.

“After considering the totality of the available scientific evidence and the deliberations of our advisory committee of independent, external experts, the FDA amended the EUA for the Pfizer-BioNTech COVID-19 vaccine to allow for a booster dose in certain populations such as health care workers, teachers and daycare staff, grocery workers and those in homeless shelters or prisons, among others,” Acting FDA Commissioner Janet Woodcock, MD, said in a news release.

The recommendations align with those from an FDA advisory panel Sept. 17.

The agency determined that the benefits of a booster dose outweigh the risks for people now authorized to receive it, according to the news release.
 

Other questions remain

So, how will this work? That was the main question weighing on the minds of the CDC’s ACIP during their first day of a 2-day meeting where they are expected to make recommendations on booster doses for Americans.

The panel discussed situations the FDA will still need to consider, such as what should be done for Americans who were originally vaccinated with a Moderna or Johnson and Johnson vaccine, but are not covered under the revised EUA, which is only for those people who received Pfizer’s two-dose vaccine regimen.

“That’s going to leave half of the people immunized in this age group having received the vaccine and being told that they’re at risk now for waning immunity and hospitalization unable to get a booster dose,” said committee member Sarah S. Long, MD, a professor of pediatrics at Drexel University College of Medicine in Philadelphia. “So that’s a big public health panic that we would like to avoid.”

Johnson and Johnson recently reported that second doses of its vaccine boosted its efficacy to almost 94% against COVID-19. A new study, published ahead of peer review, suggests that the efficacy of the single-dose Johnson and Johnson shot has fallen to about 78% against symptomatic infection during the Delta surge.

Moderna has applied for permission to market third doses of its vaccine in the United States, but the FDA has given no timeline on when it might make a decision. 

Doran Fink, MD, PhD, deputy director of the FDA’s Division of Vaccines and Related Products Applications, a representative advising the committee Sept. 22, said the agency was working as rapidly as possible on Moderna’s submission.

Regarding the question of whether it was OK to mix vaccines, rather than match them, Dr. Fink said there are currently not enough data available to inform that decision.

Those answers are coming, though. John Beigel, MD, associate director of clinical research at the National Institute of Allergy and Infectious Diseases, revealed that the federal government has a study underway to see what happens when the vaccines are mixed with each other. 

He said that data from the study would be available later this fall, and would certainly help physicians and other healthcare providers know whether it’s effective or safe to use them interchangeably.
 

Correlates of immunity

The ACIP left much of its schedule open Sept. 23 to discuss extra Pfizer doses and vote on how they should be used.

Pfizer had originally applied to the FDA for an amendment to its FDA approval, which would have given doctors a freer hand to prescribe third doses as they saw fit, in patients as young as 16.

But the FDA’s Vaccines and Related Biological Products Advisory Committee voted Sept. 17 against granting the amendment. The committee was particularly concerned about the lack of data in teens ages 16 and 17, who have the highest risk for a rare side effect that causes heart inflammation that requires hospital care.

Instead, they recommended — and the FDA agreed per their decision Sept. 22 — that third doses should be given to people at higher risk for severe breakthrough infections because of advanced age or because they work in an occupation that puts them at high risk for exposure. 

The CDC panel heard important presentations on new science that is helping to identify the correlates of immunity. 

The correlates of immunity are biomarkers that can be measured in blood that help doctors understand how protected a person may be against COVID-19. These markers of immunity are not yet known for the COVID-19 vaccines.

Emerging evidence shows that booster doses of the Pfizer vaccine cause front-line immune defenders — called binding antibodies — to roughly triple soon after a person gets the third shot. 

Neutralizing antibodies also jump soon after two vaccine doses, but they fall over time, which is natural. The body doesn’t need these foot soldiers to be on guard all the time, so they go away. 

The body retains its memory of how to make them, however, so they can quickly be marshaled again, if needed.

Early studies suggest that antibodies account for about two thirds of a person’s protection against COVID, while the longer-lasting T-cells and B-cells account for about one third.

After the antibody levels fall, it may take a few days to recreate this army. In the meantime, the virus can try to break in. This can cause symptoms, which can make a person feel terrible, but for the most part, vaccinated individuals don’t need hospital care and are nearly always protected from dying — even against the Delta variant.

Those most likely to be at risk for a breakthrough infection are older, because immune function wanes with age.
 

Essential workers

Essential workers, such as those who work in healthcare, may also benefit from high antibody levels, which can minimize symptoms and help them get back to work more quickly.

Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, said that in her area staffing levels are critical right now.

“I’m actually sitting in one of the deepest red [states] with high rates of COVID. We don’t have enough health care workers currently to take care of the unvaccinated,” she said. 

“When we have beds, we are often missing staff, and so the idea of vaccinating health care workers is to be a little bit different than our idea of using vaccines in the general population,” Dr. Talbot said.

Oliver Brooks, MD, chief medical officer of the Watts Healthcare Corporation in Los Angeles, said he was in favor of making a public statement about the temporary nature of the potential recommendations Sept. 23, because they probably won’t cover all who might need a third shot.

“We may want to go on record stating what it is that would allow us to broaden our recommendation or restrict our recommendation,” Dr. Brooks said.

The considerations of who should get an extra dose are not always straightforward.

New modeling by the Harvard TH Chan School of Public Health and the CDC to assist the government’s decisions on boosters had a surprise finding: in nursing homes, it’s more effective to vaccinate healthcare workers than it is to give booster doses to these residents. Nursing homes are at the mercy of community transmission. 

In regions with high transmission, it’s easy for a caregiver to bring the virus into a facility — so the models found that the transmission from these workers is a more effective strategy than giving third doses to the already highly vaccinated group of seniors who live in them.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration (FDA) late Sept. 22 granted emergency use authorization (EUA) for a third dose of the Pfizer COVID-19 vaccine for those over the age of 65 and a wide swath of Americans at higher risk for infection.

The agency’s move comes as a Centers for Disease Control and Prevention (CDC) panel ended the first day of a 2-day meeting. That panel, the Advisory Committee on Immunization Practices (ACIP), is expected to vote Sept. 23 to instruct doctors on how to administer the boosters.

The FDA officially authorized the vaccine not only for individuals 65 and older, but also for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers whose jobs increase their risk for infection.

“After considering the totality of the available scientific evidence and the deliberations of our advisory committee of independent, external experts, the FDA amended the EUA for the Pfizer-BioNTech COVID-19 vaccine to allow for a booster dose in certain populations such as health care workers, teachers and daycare staff, grocery workers and those in homeless shelters or prisons, among others,” Acting FDA Commissioner Janet Woodcock, MD, said in a news release.

The recommendations align with those from an FDA advisory panel Sept. 17.

The agency determined that the benefits of a booster dose outweigh the risks for people now authorized to receive it, according to the news release.
 

Other questions remain

So, how will this work? That was the main question weighing on the minds of the CDC’s ACIP during their first day of a 2-day meeting where they are expected to make recommendations on booster doses for Americans.

The panel discussed situations the FDA will still need to consider, such as what should be done for Americans who were originally vaccinated with a Moderna or Johnson and Johnson vaccine, but are not covered under the revised EUA, which is only for those people who received Pfizer’s two-dose vaccine regimen.

“That’s going to leave half of the people immunized in this age group having received the vaccine and being told that they’re at risk now for waning immunity and hospitalization unable to get a booster dose,” said committee member Sarah S. Long, MD, a professor of pediatrics at Drexel University College of Medicine in Philadelphia. “So that’s a big public health panic that we would like to avoid.”

Johnson and Johnson recently reported that second doses of its vaccine boosted its efficacy to almost 94% against COVID-19. A new study, published ahead of peer review, suggests that the efficacy of the single-dose Johnson and Johnson shot has fallen to about 78% against symptomatic infection during the Delta surge.

Moderna has applied for permission to market third doses of its vaccine in the United States, but the FDA has given no timeline on when it might make a decision. 

Doran Fink, MD, PhD, deputy director of the FDA’s Division of Vaccines and Related Products Applications, a representative advising the committee Sept. 22, said the agency was working as rapidly as possible on Moderna’s submission.

Regarding the question of whether it was OK to mix vaccines, rather than match them, Dr. Fink said there are currently not enough data available to inform that decision.

Those answers are coming, though. John Beigel, MD, associate director of clinical research at the National Institute of Allergy and Infectious Diseases, revealed that the federal government has a study underway to see what happens when the vaccines are mixed with each other. 

He said that data from the study would be available later this fall, and would certainly help physicians and other healthcare providers know whether it’s effective or safe to use them interchangeably.
 

Correlates of immunity

The ACIP left much of its schedule open Sept. 23 to discuss extra Pfizer doses and vote on how they should be used.

Pfizer had originally applied to the FDA for an amendment to its FDA approval, which would have given doctors a freer hand to prescribe third doses as they saw fit, in patients as young as 16.

But the FDA’s Vaccines and Related Biological Products Advisory Committee voted Sept. 17 against granting the amendment. The committee was particularly concerned about the lack of data in teens ages 16 and 17, who have the highest risk for a rare side effect that causes heart inflammation that requires hospital care.

Instead, they recommended — and the FDA agreed per their decision Sept. 22 — that third doses should be given to people at higher risk for severe breakthrough infections because of advanced age or because they work in an occupation that puts them at high risk for exposure. 

The CDC panel heard important presentations on new science that is helping to identify the correlates of immunity. 

The correlates of immunity are biomarkers that can be measured in blood that help doctors understand how protected a person may be against COVID-19. These markers of immunity are not yet known for the COVID-19 vaccines.

Emerging evidence shows that booster doses of the Pfizer vaccine cause front-line immune defenders — called binding antibodies — to roughly triple soon after a person gets the third shot. 

Neutralizing antibodies also jump soon after two vaccine doses, but they fall over time, which is natural. The body doesn’t need these foot soldiers to be on guard all the time, so they go away. 

The body retains its memory of how to make them, however, so they can quickly be marshaled again, if needed.

Early studies suggest that antibodies account for about two thirds of a person’s protection against COVID, while the longer-lasting T-cells and B-cells account for about one third.

After the antibody levels fall, it may take a few days to recreate this army. In the meantime, the virus can try to break in. This can cause symptoms, which can make a person feel terrible, but for the most part, vaccinated individuals don’t need hospital care and are nearly always protected from dying — even against the Delta variant.

Those most likely to be at risk for a breakthrough infection are older, because immune function wanes with age.
 

Essential workers

Essential workers, such as those who work in healthcare, may also benefit from high antibody levels, which can minimize symptoms and help them get back to work more quickly.

Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, said that in her area staffing levels are critical right now.

“I’m actually sitting in one of the deepest red [states] with high rates of COVID. We don’t have enough health care workers currently to take care of the unvaccinated,” she said. 

“When we have beds, we are often missing staff, and so the idea of vaccinating health care workers is to be a little bit different than our idea of using vaccines in the general population,” Dr. Talbot said.

Oliver Brooks, MD, chief medical officer of the Watts Healthcare Corporation in Los Angeles, said he was in favor of making a public statement about the temporary nature of the potential recommendations Sept. 23, because they probably won’t cover all who might need a third shot.

“We may want to go on record stating what it is that would allow us to broaden our recommendation or restrict our recommendation,” Dr. Brooks said.

The considerations of who should get an extra dose are not always straightforward.

New modeling by the Harvard TH Chan School of Public Health and the CDC to assist the government’s decisions on boosters had a surprise finding: in nursing homes, it’s more effective to vaccinate healthcare workers than it is to give booster doses to these residents. Nursing homes are at the mercy of community transmission. 

In regions with high transmission, it’s easy for a caregiver to bring the virus into a facility — so the models found that the transmission from these workers is a more effective strategy than giving third doses to the already highly vaccinated group of seniors who live in them.

A version of this article first appeared on Medscape.com.